Palmitoleic acid (also known as 9-hexadecenoic acid and C16:1 n-7) is an omega-7 monounsaturated fatty acid having the formula CH3(CH2)5CH═CH(CH2)7COOH. Palmitoleic acid can occur in a cis or trans configuration. In its cis configuration, palmitoleic acid is a common constituent of the glycerides of human adipose (fat) tissue and is found in the lipid bilayer of the cell membrane in all human tissues where it can participate in several metabolic processes.
Myristoleic acid (also known as 9-tetradecenoic acid and C14:1 n-5) is an omega-5 fatty acid produced in nature by the action of delta-9 desaturase on myristic acid. This fatty acid (cis-form) is relatively uncommon in nature. Low concentrations (between 1% and 2%) of myristoleic acid are found in fish oils and dairy butter; however, myristoleic acid is present in quite high concentration in the seed oil from plants of the genus Myristicaceae. Myristoleic acid has anti-inflammatory and analgesic properties and appears to slow prostate tumor growth. Omega-5 fatty acids are understood to be effective in treating and/or preventing a variety of diseases including cardiovascular and skin disorders as well as certain types of cancer as well as certain psychiatric and cognitive disorders.
Lauroleic acid (also known as 9-dodecenoic acid and C12:1 n-3) is an omega-3 fatty acid. This fatty acid (cis-form) is also relatively uncommon in nature, found in small amounts in animal fats and milk lipids. Lauroleic acid is a natural metabolite of lauric acid in rat hepatocytes (Legrand P et al., Lipids, 37:569 (2002)). Omega-3 fatty acids are understood to be effective in treating cardiovascular, inflammation and cancer
Recent studies indicate that cis-palmitoleic acid may have protective effects against some cardiovascular disease risk factors. For example, higher concentration of circulating cis-palmitoleic acid is associated with lower LDL cholesterol (often referred to as “bad” cholesterol), higher HDL cholesterol (often referred to as “good” cholesterol), and lower total HDL-cholesterol ratio. (Mozaffarian et al., Am. J. Clin. Nutr., 92(6):1350-1358 (2010)). Published data show that diets enriched for macadamia nuts, a rich natural source of cis-palmitoleic acid, result in significantly lower plasma total cholesterol and LDL cholesterol in men and women and in controlled lab animal studies (Curb et al., Arch. Intern. Med., 160:1154-1158 (2000); Matthan et al, J. Nutr., 139(2):215-221 (2009); Griel et al., J. Nutr., 138:761-767 (2008)). The hypocholesterolemic effect of dietary monounsaturated fatty acids such as cis-palmitoleic acid has been attributed to up-regulation of LDL receptor activity. Monounsaturated fatty acids are preferred substrates for acyl CoA:cholesterol acyltransferase, which catalyzes the esterification of hepatic free cholesterol to an inert cholesterol ester pool. This in turn reduced the putative regulatory pool of intracellular free cholesterol, increasing LDL receptor activity and subsequently decreasing circulating cholesterol concentrations (Griel et al., 2008; Mozaffarian, 2010).
Studies also indicate that cis-palmitoleic aid promotes beta-cell proliferation, and facilitates production of glucagon-like peptide-1 (GLP-1), an incretin hormone that enhances the glucose-dependent secretion of insulin from Beta-cells. (Maedler et al., Diabetes, 50:69-76 (2001)); Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120 (Hirasawa et al., Nature Medicine, 11(1):90-94 (2005)). Increased cis-palmitoleic acid level is also observed in the newborn in response to oxidative stress. (Hara et al., Biochemical and Biophysical Research Communications, 257(1):244-248 (1999)).
Recent studies have found that trans-palmitoleic acid levels are inversely associated with new-onset (type 2) diabetes and other metabolic risk factors and tends to promote healthy levels of blood cholesterol (Mozaffarian et al., Ann. Intern. Med., 153(12):790-799 (2010)). Moreover, the trans-configuration of palmitoleic acid may be more bioactive than the cis-configuration.
Cis-palmitoleic acid can be obtained in the diet, e.g. from fish, plants and nuts enriched for this fatty acid. For example, buckthorn oil and macademia oil are known to be enriched for cis-palmitoleic acid. Alternatively, extracts containing cis-palmitoleic acid can be obtained from marine or aquatic biomass as described in U.S. Patent Appl. Pub. No. 2004/0234587, the contents of which are incorporated herein by reference. Trans-palmitoleic acid is not endogenously produced in humans but is a component of dairy products such as milk, yogurt and cheese; accordingly, extracts containing trans-palmitoleic acid may be obtained from these sources.
Fatty acids in the form of phospholipids are reported to be more readily absorbed and also to be more bioactive. Palmitoleic acid, myristoleic acid and lauroleic acid obtained from fish or plant extract is not especially suitable for use in the modern food/medicine industries. For example, cis-palmitoleic acid, in the form of phospholipid, is present as only a small percentage of the total lipids found in fish, plants or nuts enriched for this fatty acid. Moreover, phospholipids extracted from natural sources, especially marine sources, come with characteristic tastes and smell which reduces their appeal in food applications.
Therefore, there is a need for compositions having a relatively high bioavailable concentration of palmitoleic acid, myristoleic acid and lauroleic acid in the form of phospholipid, and a commercially viable method for its production.